Individual OI and MR perfusion values at baseline and follow-up (therapy group).

<p>^abaseline</p><p>^bfollow-up; SE = standard error</p><p>*p < 0.05 (follow-up vs. baseline)</p><p>Note the significant increase of apoptosis-targeted OI signal and the significant plasma flow (PF) reduction in the therapy group (p < 0.05).</p

Individual OI and MR perfusion values at baseline and follow-up (control group).

<p>^abaseline</p><p>^bfollow-up; SE = standard error</p><p>*p < 0.05 (follow-up vs. baseline)</p><p>Note the omnidirectional development of individual apoptosis-targeted OI signal and perfusion parameters.</p

<i>Ex vivo</i> OI analysis of explanted main organs.

<p>Fusion of color-coded fluorescence and anatomic white-light image. In accordance with the in vivo results, highest OI signal is observed in the kidneys (1) and the tumor (2) (red arrows). As a blood pool organ, the spleen (3) demonstrates relatively high probe accumulation. Only subtle OI signal is detected in the gut (4), the skin (5), and the thigh muscle (6). OI signal intensity (SI) is displayed in arbitrary units (a.u.).</p

Representative immunohistochemical stainings.

<p>Tumor cell apoptosis (TUNEL, A and B), tumor microvascular density (CD31, C and D), and tumor cell proliferation (Ki-67, E and F) in the control (left column; A, C, and E) and the therapy group (right column; B, D, and F). Note the significantly higher apoptosis rate (B vs. A) as well as the significantly lower microvascular density (D vs. C) and proliferation (F vs. E) in the therapy group.</p

Decrease of tumor perfusion following anti-angiogenic therapy.

<p>Tumor perfusion (Plasma Flow, PF) before (A) and after (B) a one-week regorafenib treatment of a subcutaneous colon carcinoma xenografts over the left abdominal flank. Note the significantly reduced plasma flow after therapy (B vs. A).</p

Cell death-related OI signal before and after treatment.

<p>Fusion of color-coded fluorescence and anatomic white-light image of one animal before (A) and after (B) a one-week regorafenib monotherapy. Note the significant increase in cell death-related signal under therapy, predominantly in the center of the tumor. High signal intensity is also observed in the kidneys and the urinary bladder due to renal probe elimination. OI signal intensity (SI) is displayed in arbitrary units (a.u.).</p

Individual immunohistochemical values in the control (animals no. 1 to 8) and the therapy group (animals no. 9 to 16).

<p>SE = standard error</p><p>*p < 0.05 (control vs. therapy group)</p><p>Note the significantly lower microvascular density (CD31) and proliferation (Ki-67) as well as the significantly higher apoptosis rate in the therapy group (p < 0.05).</p

Individual DCE-MRI values.

<p>Individual DCE-MRI values.</p

Representative CEUS images of a rat with a subcutaneous tumor xenograft (white arrows) under treatment.

<p>Therapy group (red) and control group (blue) at baseline and follow-up. Left side: early vascular phase with BR55 as a functional imaging biomarker; right side: late phase of VEGFR2-specific binding with BR55 as a molecular imaging biomarker 8 minutes after contrast injection. Note the significant lower number of circulating microbubbles in the early vascular phase as well as the significant lower number of bound microbubbles in the late phase at follow-up in the therapy group, compared to baseline and compared to the control group.</p

Individual molecular CEUS values.

<p>Individual molecular CEUS values.</p